Abstract
Background
Although basic research has suggested that oxidized low-density lipoprotein (ox-LDL)
is involved in the pathogenesis of atherosclerosis, population observational studies
have yielded conflicting results about the association between circulating ox-LDL
and atherosclerotic cardiovascular disease (ASCVD). Therefore, we performed a systematic
review and meta-analysis of currently available observational studies to verify the
association between circulating ox-LDL and ASCVD.
Methods
We systematically searched PubMed and the Cochrane Library from their inception to
March 27, 2017, for nested case-control studies, case-cohort studies, and prospective
cohort studies on the relationship between ox-LDL and ASCVD. Studies that did not
assess the hazard ratio, relative risk, or odds ratio of ox-LDL or did not adjust
for other risk factors, or those without examination of ox-LDL before collection of
ASCVD occurrences were excluded. The summarized effect size was combined using fixed
effect models. Subgroup analyses were performed on the basis of study quality, study
design, definition of ASCVD events, effect size types, types of ox-LDL assay, ox-LDL
contrast level, and whether low-density lipoprotein cholesterol was adjusted in a
multivariate model.
Results
A total of 12 included studies consisted of 3 nested case-control studies, 1 case-cohort
study, 5 hospital-based cohort studies, and 3 community-based cohort studies. The
summary effect size of increased circulating ox-LDL was 1.79 (95% confidence interval,
1.56-2.05) for ASCVD. Similar associations were shown in all subgroups.
Conclusions
Our findings indicate that increased levels of circulating ox-LDL are associated with
clinical ASCVD events. Further well designed community-based cohort studies or intervention
studies are needed to confirm our findings.
Résumé
Contexte
Même si la recherche fondamentale suggère que les lipoprotéines de faible densité
(LDL) oxydées jouent un rôle dans la pathogenèse de l’athérosclérose, des études observationnelles
de population ont abouti à des résultats contradictoires en ce qui concerne le lien
entre les LDL oxydées circulantes et les maladies cardiovasculaires (MCV) athéroscléreuses.
C’est pourquoi nous avons effectué une revue et une méta-analyse systématiques des
études observationnelles disponibles à ce jour pour vérifier le lien entre les LDL
oxydées circulantes et les MCV athéroscléreuses.
Méthodologie
Nous avons réalisé une recherche systématique dans PubMed et la bibliothèque Cochrane
à partir du moment de leur création jusqu’au 27 mars 2017, et ce, afin de trouver
des études de cas-témoins emboîtés, des études cas-cohortes et des études de cohortes
prospectives évaluant le lien entre les LDL oxydées circulantes et les MCV athéroscléreuses.
Les études suivantes ont été exclues : celles qui n’ont pas évalué le rapport des
risques instantanés, le risque relatif ou le rapport de cotes relativement aux LDL
oxydées; celles qui n’ont pas ajusté les résultats en fonction d’autres facteurs de
risque; ou celles qui n’ont pas évalué le taux de LDL oxydées avant de relever la
survenue de manifestations attribuables aux MCV athéroscléreuses. L’ampleur globale
de l’effet a été obtenue en utilisant des modèles à effets fixes. Des analyses de
sous-groupes ont été réalisées en se basant sur la qualité de l’étude, la méthodologie,
la définition des manifestations attribuables aux MCV athéroscléreuses, le type d’ampleur
de l’effet, le type d’analyses pour mesurer le taux de LDL oxydées, le niveau de contraste
lié aux LDL oxydées, et si le taux de cholestérol LDL a été ajusté selon un modèle
multivarié.
Résultats
Au total, 12 études ont été prises en compte, soit 3 études de cas-témoins emboîtés,
1 étude cas-cohortes, 5 études de cohortes hospitalières et 3 études de cohortes communautaires.
L’ampleur de l’effet globale de l’augmentation des LDL oxydées dans le sang était
de 1,79 (intervalle de confiance à 95 % : 1,56-2,05) pour les MCV athéroscléreuses.
Un lien similaire a été observé dans tous les sous-groupes.
Conclusion
Nos résultats montrent qu’un taux circulant élevé de LDL oxydées est associé à des
manifestations cliniques attribuables aux MCV athéroscléreuses. D’autres études de
cohortes communautaires ou études d’intervention bien conçues seront nécessaires pour
confirmer nos résultats.
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Article info
Publication history
Published online: July 28, 2017
Accepted:
July 20,
2017
Received:
May 4,
2017
Footnotes
See editorial by Arsenault et al., pages 1513–1516 of this issue.
See page 1631 for disclosure information.
Identification
Copyright
© 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
